Lung transplantation is often the only treatment option for individuals with end-stage lung diseases. However, chronic allograft rejection, which manifests as bronchiolitis obliterans (OB), is the major cause of death beyond the first year following transplantation, and a major contributor to the currently low 5 year survival rate (55%). OB is characterized by airflow limitation that is not reversible and is often progressive. It is also associated with lesions in the smallest airways (˜1 mm). Despite advancements in immunosuppression and management of these patients, OB remains a major obstacle in the survival of lung transplant recipients. Thus, there is an unmet need to define immunomodulatory strategies in the lung transplant population which can be provided at a low systemic toxicity risk, yet be delivered to specific target regions at high therapeutic concentrations.
Cell-based therapy shows considerable potential as an immunomodulatory strategy for a variety of lung diseases. Novel techniques to target delivery of these therapies by inhaled aerosol would avoid first-pass metabolism, prevent systemic toxicity, and allow for localized treatment in the small airways at the site of OB.